Chapter 14 - Association of phospholipase C and D in cardiovascular risk prediction and progression

Abstract

Phospholipids are major structural components of the cell membrane involved in responding to various molecular and cellular stimuli. Phospholipases (PLs) are of three different types, namely PLA, PLC, and PLD, which are involved in the catalysis of breakdown of phospholipids. In the heart, PL activates several intracellular signal transduction pathways involved in cardiac contraction: growth/proliferation of vascular smooth muscle cells (VSMC), myocardial membrane functioning, etc. Thus the dysregulation of PL can contribute to several diseases including the development and progression of cardiovascular diseases (CVD). Cardiomyocytes expresses different types of PLC while protein kinase C (PKC) and small G proteins stimulate PLD activity in cardiomyocytes. PLC regulates monocyte/macrophage interaction with endothelial cells, cytokine production, dendritic cell migration, foam cell formation, and activation and development of immune cells, which are manifestations of atherosclerosis. PLC can be a better diagnostic marker for atherosclerosis. PLC is considered to be associated with enhanced calcium ion activation, vascular endothelial growth factors (VEGF), MAP kinase signaling leading to coronary artery spasm, cardiac vascularization, hypertension, and other cardiac diseases. PLD-induced cellular necrosis, apoptosis, and ventricular fibrosis lead to major cardiovascular events. PLC activators and inhibitors have been shown to be a favorable target for drug development. However, further studies focusing on PLC and PLD signaling in the progression, development, and risk stratification of CVD needs to be extensively done. Pharmacological inhibitors for PLC and PLD with better specificity have to be developed further, which may open new avenues for the prevention and treatment of CVDs.